Research Topic

Neuroimmune interaction in the skin

About this Research Topic

The skin is densely innervated by peripheral nerves and is the critical location for the nerve meshwork, including sensory nerves, sympathetic and parasympathetic nerves. Various peripheral nerves execute distinct roles in transmitting efferent and afferent signals between the central nervous system and the innervated areas. Nociceptors for example, specialized peripheral sensory neurons, transduce noxious stimuli in receptor potentials. These nerve cell endings detect potentially damaging stimuli, and convey the information centrally. The past few decades have seen major advances in the fields of immunology and neuroscience in understanding the biology of skin immunity and innerved neurons.

Recent evidence suggests that both the immune and nervous systems are engaged in immune defense and inflammation. For example, nociceptors can regulate both anti-bacterial immune response and psoriatic inflammation in different immune settings: Stimulation of the TrpV1 sensory neurons could promote a type 17 immune response and augment the anti-fungal and anti-bacterial defense; the C albicans-induced inflammation was exaggerated upon depletion of the nociceptive sensory neurons; and the psoriasiform cutaneous inflammation was reduced upon ablation of nociceptive sensory neurons, accounted for by decreased induction of interleukin-23 in the dermal dendritic cell upon Imiquimod administration. In addition, they can be directly activated by bacteria-derived components or modulated by the inflammation induced cytokine release: the bacterial pore-forming toxin could directly activate sensory neurons; a plethora of cytokines have been found to signal through their receptors expressed on the sensory neurons. However, our knowledge regarding the crosstalk is far from complete.

The skin is a unique niche as the front line for the host-environment exchange. Sensory and autonomic nerves are often found in proximity to immune cells at the skin barrier. The combination of nerve endings including Ab, Ad or C are all present in the skin, primarily detecting a complex spectrum of sensory stimuli, such as temperature and pressure. The activation of sensory receptors following stimulation, and consequent neurotransmitter release, and signal transduction activation, promotes the start of the communication between the nervous system and the immune system.

Multiple cell types have been shown to be regulated by peripheral nerves, such as gammadelta T cells, dermal dendritic cells, Langerhans cells. MAST cells for example, are directly regulated by neuropeptides of CGRP that play an important role in pain mechanisms, VIP, and unknown neurotransmitters.

In-depth studies of the neuroimmune dialogue mechanisms and the mediators regulating this reciprocal interaction, will provide us critical information on how neurons may regulate immunity and how the immune homeostasis and dysregulation may influence the nervous system in turn.

This Research Topic is hoping to enhance our understanding of how the nervous and immune system may interact, providing grounds to explore the neuroimmune connectome fast-evolving field with an eye of focus to skin immune response following neuroimmune dialogue.
We welcome authors to contribute with research articles, reviews, and perspectives, addressing the following, but not limited to, themes:

• neuronal regulation of skin immunity – cross-talk mediators and their action
• Neuroinflammation mechanism - response coordination between nervous system and immune system
• Reciprocal crosstalk of peripheral nerves such as nociceptors and the skin immune responses

Besides, a dedicated column will be established to promote images and videos regarding skin neuroimmune communications. The cutting-edge images and videos will help to develop the physical landscape of the emerging concept of “neuroimmune connectome”.


Keywords: Nervous system, skin immunity, infection, allergy, inflammation


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

The skin is densely innervated by peripheral nerves and is the critical location for the nerve meshwork, including sensory nerves, sympathetic and parasympathetic nerves. Various peripheral nerves execute distinct roles in transmitting efferent and afferent signals between the central nervous system and the innervated areas. Nociceptors for example, specialized peripheral sensory neurons, transduce noxious stimuli in receptor potentials. These nerve cell endings detect potentially damaging stimuli, and convey the information centrally. The past few decades have seen major advances in the fields of immunology and neuroscience in understanding the biology of skin immunity and innerved neurons.

Recent evidence suggests that both the immune and nervous systems are engaged in immune defense and inflammation. For example, nociceptors can regulate both anti-bacterial immune response and psoriatic inflammation in different immune settings: Stimulation of the TrpV1 sensory neurons could promote a type 17 immune response and augment the anti-fungal and anti-bacterial defense; the C albicans-induced inflammation was exaggerated upon depletion of the nociceptive sensory neurons; and the psoriasiform cutaneous inflammation was reduced upon ablation of nociceptive sensory neurons, accounted for by decreased induction of interleukin-23 in the dermal dendritic cell upon Imiquimod administration. In addition, they can be directly activated by bacteria-derived components or modulated by the inflammation induced cytokine release: the bacterial pore-forming toxin could directly activate sensory neurons; a plethora of cytokines have been found to signal through their receptors expressed on the sensory neurons. However, our knowledge regarding the crosstalk is far from complete.

The skin is a unique niche as the front line for the host-environment exchange. Sensory and autonomic nerves are often found in proximity to immune cells at the skin barrier. The combination of nerve endings including Ab, Ad or C are all present in the skin, primarily detecting a complex spectrum of sensory stimuli, such as temperature and pressure. The activation of sensory receptors following stimulation, and consequent neurotransmitter release, and signal transduction activation, promotes the start of the communication between the nervous system and the immune system.

Multiple cell types have been shown to be regulated by peripheral nerves, such as gammadelta T cells, dermal dendritic cells, Langerhans cells. MAST cells for example, are directly regulated by neuropeptides of CGRP that play an important role in pain mechanisms, VIP, and unknown neurotransmitters.

In-depth studies of the neuroimmune dialogue mechanisms and the mediators regulating this reciprocal interaction, will provide us critical information on how neurons may regulate immunity and how the immune homeostasis and dysregulation may influence the nervous system in turn.

This Research Topic is hoping to enhance our understanding of how the nervous and immune system may interact, providing grounds to explore the neuroimmune connectome fast-evolving field with an eye of focus to skin immune response following neuroimmune dialogue.
We welcome authors to contribute with research articles, reviews, and perspectives, addressing the following, but not limited to, themes:

• neuronal regulation of skin immunity – cross-talk mediators and their action
• Neuroinflammation mechanism - response coordination between nervous system and immune system
• Reciprocal crosstalk of peripheral nerves such as nociceptors and the skin immune responses

Besides, a dedicated column will be established to promote images and videos regarding skin neuroimmune communications. The cutting-edge images and videos will help to develop the physical landscape of the emerging concept of “neuroimmune connectome”.


Keywords: Nervous system, skin immunity, infection, allergy, inflammation


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

11 January 2021 Manuscript
10 February 2021 Manuscript Extension

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

11 January 2021 Manuscript
10 February 2021 Manuscript Extension

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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